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World J Gastroenterol. Apr 14, 2017; 23(14): 2505-2510
Published online Apr 14, 2017. doi: 10.3748/wjg.v23.i14.2505
New progress in roles of nitric oxide during hepatic ischemia reperfusion injury
Ya-Qi Zhang, Ning Ding, Yong-Fen Zeng, Yuan-Yuan Xiang, Mei-Wen Yang, Fen-Fang Hong, Shu-Long Yang
Ya-Qi Zhang, Ning Ding, Yong-Fen Zeng, Yuan-Yuan Xiang, Mei-Wen Yang, Shu-Long Yang, Department of Physiology, Basic Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China
Fen-Fang Hong, Medical Experimental Teaching Center, Jiangxi Medical College, Nanchang University, Nanchang 330031, Jiangxi Province, China
Author contributions: Zhang YQ, Ding N, Zeng YF and Xiang YY contributed equally to this work, and they wrote the paper; Yang MW contributed to data collection and paper revision; Hong FF and Yang SL also contributed equally to this work, they are responsible for the idea, fund and the paper revision.
Supported by National Natural Science Foundation of China, No. 81260504, No. 81660151 and No. 81660751; Science Foundation of Science Commission of Jiangxi Province, China, No. 20161BBG70067; School Teaching Reform Fund of Nanchang University, No. NCUJGLX - 14-1-111.
Conflict-of-interest statement: There is no conflict of interest associated with any of the authors in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shu-Long Yang, PhD, Professor, Department of Physiology, Basic Medical College, Nanchang University, 461 Bayi Road, Nanchang 330006, Jiangxi Province, China. slyang@ncu.edu.cn
Telephone: +86-791-86360556 Fax: +86-791-86360556
Received: December 6, 2016
Peer-review started: December 8, 2016
First decision: December 30, 2016
Revised: January 11, 2017
Accepted: February 16, 2017
Article in press: February 16, 2017
Published online: April 14, 2017
Processing time: 129 Days and 6.3 Hours
Abstract

Hepatic ischemia reperfusion injury (HIRI) is a clinical condition which may lead to cellular injury and organ dysfunction. The role of nitric oxide (NO) in HIRI is complicated and inconclusive. NO produced by endothelial nitric oxide synthase (eNOS) activation plays a protective role during early HIRI. But eNOS overexpression and the resulting excessive NO bioavailability can aggravate liver injury. NO induced by inducible nitric oxide synthase (iNOS) may have either a protective or a deleterious effect during the early phase of HIRI, but it may protect the liver during late HIRI. Here, we reviewed the latest findings on the role of NO during HIRI: (1) NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS via inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; (2) eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1α-eNOS/NO) participating in the anti-HIRI process, and inhibiting over-expression of eNOS also protects against HIRI; and (3) the inhibition of iNOS prevents HIRI. Thus, the adverse effects of NO should be avoided, but its positive effect in the clinical treatment of diseases associated with HIRI should be recognized.

Keywords: Liver; Hepatic ischemia reperfusion injury; Nitric oxide; Nitric oxide synthase

Core tip: The latest findings on the role of nitric oxide (NO) during hepatic ischemia reperfusion injury (HIRI) include: NO exerts a protective effect against HIRI by increasing NO bioavailability, downregulating p53 gene expression, decreasing inflammatory chemokines, reducing ROS by inhibiting the mitochondrial respiratory chain, activating sGC-GTP-cGMP signal pathway to reduce liver cell apoptosis, and regulating hepatic immune functions; eNOS protects against HIRI by increasing NO levels, several eNOS/NO signal pathways (such as Akt-eNOS/NO, AMPK-eNOS/NO and HIF-1α-eNOS/NO) participating in the anti-HIRI process; inhibiting over-expression of eNOS also protects against HIRI; and finally, the inhibition of iNOS prevented HIRI.